Researchers use nanoscale 'patches' to sensitize targeted cell receptors

November 25, 2013 by Matt Shipman

Researchers from North Carolina State University and Duke University have developed nanoscale "patches" that can be used to sensitize targeted cell receptors, making them more responsive to signals that control cell activity. The finding holds promise for promoting healing and facilitating tissue engineering research.

The research takes advantage of the fact that cells in a living organism can communicate via physical contact. Specifically, when targeted on the surface of a cell are triggered, the cell receives instructions to alter its behavior in some way. For example, the instructions may cause a stem cell to differentiate into a bone cell or a cartilage cell.

These receptors respond to specific ligands, or target molecules. And those ligands have to be present in certain concentrations in order to trigger the receptors. If there aren't enough target ligands, the receptors won't respond.

Now researchers have developed nanoscale patches that are embedded with tiny protein fragments called . These peptides bond to a specific , making it more sensitive to its target ligand – meaning that it takes fewer ligand molecules to trigger the receptor and its resulting behavior modification.

"This study shows that our concept can work, and there are a host of potential applications," says Dr. Thom LaBean, an associate professor of materials science at NC State and senior author of a paper describing the work. "For example, if we identify the relevant peptides, we could create patches that sensitize cells to promote cartilage growth on one side of the patch and bone growth on the other side. This could be used to expedite healing or to enable of biomedical implants."

"What's important about this is that it allows us to be extremely precise in controlling cell behavior and gene expression," says Ronnie Pedersen, a Ph.D. student at Duke University and lead author of the paper. "By controlling which peptides are on the patch, we can influence the cell's activity. And by manipulating the placement of the patch, we can control where that activity takes place."

The patch itself is made of DNA that researchers have programmed to self-assemble into flexible, two-dimensional sheets. The sheets themselves incorporate molecules called biotin and streptavidin which serve to hold and organize the peptides that are used to sensitize cell receptors.

"These peptides can bind with cell receptors and sensitize them, without blocking the interaction between the receptors and their target ligands," Pedersen says. "That's what makes this approach work."

Explore further: Breast stem-cell research: Receptor teamwork is required and a new pathway may be involved

More information: The paper, "Sensitization of Transforming Growth Factor-β Signaling by Multiple Peptides Patterned on DNA Nanostructures," was published online Nov. 8 in the journal Biomacromolecules. pubs.acs.org/doi/abs/10.1021/bm4011722

Abstract
We report sensitization of a cellular signaling pathway by addition of functionalized DNA nanostructures. Signaling by transforming growth factor β (TGFβ) has been shown to be dependent on receptor clustering. By patterning a DNA nanostructure with closely spaced peptides that bind to TGF? receptor, we observe increased sensitivity of NMuMG cells to TGFβ ligand. This is evidenced by translocation of secondary messenger proteins to the nucleus and stimulation of an inducible luciferase reporter at lower concentrations of TGFβ ligand. We believe this represents an important initial step toward realization of DNA as a self-assembling and biologically compatible material for use in tissue engineering and drug delivery.

Related Stories

Recommended for you

Graphene under pressure

August 25, 2016

Small balloons made from one-atom-thick material graphene can withstand enormous pressures, much higher than those at the bottom of the deepest ocean, scientists at the University of Manchester report.

Designing ultrasound tools with Lego-like proteins

August 25, 2016

Ultrasound imaging is used around the world to help visualize developing babies and diagnose disease. Sound waves bounce off the tissues, revealing their different densities and shapes. The next step in ultrasound technology ...

Nanovesicles in predictable shapes

August 25, 2016

Beads, disks, bowls and rods: scientists at Radboud University have demonstrated the first methodological approach to control the shapes of nanovesicles. This opens doors for the use of nanovesicles in biomedical applications, ...

'Artificial atom' created in graphene

August 22, 2016

In a tiny quantum prison, electrons behave quite differently as compared to their counterparts in free space. They can only occupy discrete energy levels, much like the electrons in an atom - for this reason, such electron ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.